AB0417 SHORT-TERM EFFECT OF METHOTREXATE ON APOLIPOPROTEINS AND LIPID PROFILE IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS
Authors: S. Jain, V. Dhir, B. Leishangthem, M. Kalyan, I. Verma, G. Naidu, S. K. Sharma, A. Sharma, S. Jain
Journal: Annals of the Rheumatic Diseases (2022)

Background Methotrexate (MTX) forms the first line therapy for rheumatoid arthritis (RA). The cardioprotective effect of MTX is well established, but whether this is just due to control of inflammation, or is also via an effect on serum lipoproteins, is unclear. Although a few studies have studied the effect of the MTX on the traditional lipid profile in RA 1 , there is no data on the effect of MTX on apolipoproteins (Apo A1, Apo B, ApoB/ApoA1), which are considered better cardiovascular risk predictors than the traditional lipid profile. Objectives To determine the short-term effect of MTX on apolipoproteins and traditional lipid profile in patients with active RA. Methods DMARD-naïve patients with active RA (SJC≥2 and TJC≥4) who had been enrolled in the multicentre, RCT comparing two different MTX escalation strategies in RA (MEIRA) 2 and for whom paired serum samples were available before and after MTX treatment were included. All these patients received MTX monotherapy started at 15 mg/week and escalated to 25 mg/week by 4-8 weeks. Serum levels of apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG) were measured before starting MTX and after 16 weeks of MTX monotherapy. Proatherosclerotic indices (TC/HDL and ApoB/ApoA1) were also calculated. Results A total of 103 patients [mean age 40 (8) years, 93 (90%) females, mean BMI 25.1 (4.8) kg/m 2 , all non-smokers and non-alcoholics] were included. No study participant had comorbid diabetes mellitus or coronary artery disease; none of them were taking glucocorticoids or hypolipidemic drugs. An increase in Apo A1 levels [by a mean of 5.6 mg/dL (p=0.02)], and HDL levels [by a mean of 1.6 mg/dL (p=0.04)] was seen after 16 weeks of MTX monotherapy. Although a numerical increase in levels of TC (mean 4.6 mg/dL, p=0.07), LDL (mean 2 mg/dL, p=0.34) and TG (mean 6.6 mg/dL, p=0.35) was also noted, none of these were statistically significant. No obvious change in Apo B levels and TC/HDL ratio occurred due to MTX therapy. However, the ApoB/ApoA1 ratio decreased significantly from 0.8 to 0.7 (p=0.002) with 16 weeks of MTX therapy (Table 1). Table 1. Baseline and end of treatment values of apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), and proatherosclerotic indices (TC/HDL and ApoB/ApoA1). Parameter (mg/dL) Baseline After 16 weeks of MTX therapy p-value Apo A1 126.0 (25.1) 131.6 (23.4) 0.02 Apo B 92.3 (18.9) 92.0 (20.9) 0.84 ApoB/ApoA1 0.8 (0.2) 0.7 (0.2) 0.002 TC 164.5 (32.4) 169.1 (36.8) 0.07 HDL 40.9 (9.8) 42.5 (9.7) 0.04 TC/HDL 4.2 (1.1) 4.1 (1.1) 0.34 LDL 88.8 (25.2) 90.8 (29.8) 0.34 TG 139.8 (69.6) 146.4 (91.3) 0.35 All values represented as mean (SD). Apo A1=apolipoprotein A1, ApoB=apolipoprotein B, TC=total cholesterol, LDL=low-density lipoprotein, HDL=high-density lipoprotein, TG=triglycerides Conclusion MTX therapy led to a mild but significant increase in HDL, ApoA1 and a reduction in ApoB/ApoA1 over short-term. This could potentially represent one of the mechanisms by which MTX exerts its cardioprotective effect; however, these changes need to be carefully interpreted over longer term and in context of the lipid paradox operating in RA. References [1]Navarro-Millán I, Charles-Schoeman C, Yang S, et al. Changes in lipoproteins associated with methotrexate or combination therapy in early rheumatoid arthritis: results from the treatment of early rheumatoid arthritis trial. Arthritis Rheum . 2013;65(6):1430-1438. [2]Jain S, Dhir V, Aggarwal A, et al. Comparison of two dose escalation strategies of methotrexate in active rheumatoid arthritis: a multicentre, parallel group, randomised controlled trial. Ann Rheum Dis . 2021;80(11):1376-1384. Disclosure of Interests None declared